Treatment Outcome Of Adult Newly Diagnosed Epilepsy With Normalized Management And Analysis Of Intrinsic Connectivity Network In Refractory Epilepsy

Part 1 Treatment Outcome and Risk Factors of Adult Newly Diagnosed EpilepsyObjective: The study was conducted to summarize the treatment outcomes of newly diagnosed epilepsy(NDE)and analyze the risk factors for refractory epilepsy(RE)in Northeast China.Methods: A total of 515 adult patients with NDE were consecutively enrolled in this program.Clinical data were collected at baseline and each follow-up.Several scales concerning recognition and mood were also completed at the first visit.Results: Seizure-free status was achieved by 52%(n = 265)of the patients;however,13%(n = 68)manifested RE.A total of 315(61%)patients continued with the first ASM as monotherapy,among which 187(59%)patients became seizure-free.Oxcarbazepine has the higher probability of retention and carbamazepine has the lowest one.Twenty-one(24%)patients with RE became seizure-free following ASM adjustment and 52 patients(18%)had breakthrough seizures after being classified as seizure-free.One patient developed RE after attaining seizure-free status.Breakthrough seizures during the first expected interictal interval(OR = 6.03,95% CI: 2.88-12.60),high seizure frequency at baseline(OR = 1.21,95% CI: 1.02-1.44)and younger age of onset(OR = 1.34,95% CI: 1.07-1.68)were risk factors for RE.The GAD-7 scores decrease after ASM treatment(p < 0.001).Older baseline age(B =-1.22,p <0.001),less education(B =-1.16,p <0.001)and definite etiology(B =-1.56,p = 0.001)are risk factors of lower scores of MOCA.Female gender(B = 1.93,p < 0.001)and less education(B = 0.62,p = 0.003)are risk factors of higher scores of GAD-7.Female gender(B = 1.00,p = 0.006),less education(B = 0.45,p = 0.014),high seizure frequency at baseline(B = 0.24,p = 0.044)and lower income(B = 1.22,p = 0.038)are risk factors of higher scores of c-NDDI-E.Significance: Treatment outcomes of the majority of NDE cases are good.To analyze the risk factors could help physicians more promptly and accurately identify patients who are likely to develop RE.Seizure-free state is not long enough to commence the withdrawal of ASMs.RE is not permanent and seizure-free may be achieved subsequently by appropriate drug adjustment.Part 2 Economic burden of adult newly diagnosed epilepsy in urban and rural areas in Jilin ProvinceObjective: To provide direct and indirect costs related to epilepsy in Jilin Province.Methods: Consecutive patients diagnosed with NDE in Jilin Province were included in the program and were divided into the urban group and the rural group.Direct and indirect costs were recorded prospectively and risk factors were analyzed.Result: A total of 371 patients(240 from the urban areas)were included and followed up for at least 12 months.The average annual total costs and direct costs were 4393.85 yuan and 3676.73 yuan in urban areas,and 5127.98 yuan and 3993.55 yuan in rural areas.The total and direct burdens were 12% and 9.4% in urban areas,and 28% and 209% in rural areas.The costs of the first investigation procedure were 3737.00 yuan and 3925.00 yuan in urban and rural areas,accounting for 12% and 21% of average annual family income.Rural residents(B = 0.10,p < 0.001),unemployment(B = 0.06,p = 0.007)and RE(B = 0.15,p < 0.001)were risk factors of higher direct burden.Unemployment(B=1.40,p <0.001)was the only risk factor of the higher total burden.Significance: Epilepsy lays a heavy burden on the people in Jilin Province,especially on the unemployed rural RE patients.Part 3 Alternation of intrinsic connectivity network in refractory epilepsyObjective: To analyze the intrinsic connectivity network(ICN)of conventional MRInegative RE patients.Methods: Fourteen conventional MRI-negative RE patients and 9 conventional MRI-negative SF patients were enrolled in the study.T1 weighted image(T1WI)and Echo Planar Imaging(EPI)were obtained and Mini-mental state examination(MMSE),GAD-7,c-NDDI-E and Edinburgh handness questionnaire were finished before the examination.Voxel-based morphometry(VBM),regional homogeneity(Re Ho),amplitude of low-frequency fluctuations (ALFF),and fractional ALFF(f ALFF)were compared between RE and SF patients.Independent Component Analysis was applied to extract the independent components for intranetwork and internetwork comparison.Results: The volume of grey matter of RE patients decreased in right precentral gyrus(Precentral?R)(t = 4.92,p FDR-corr = 0.020),median cingulate and paracingulate gyri(Cingulum?Mid?L?Cingulum?Mid?R)(t = 4.84,p FDR-corr = 0.012),left supplementary motor area(Supp?Motor?Area?L)(t = 7.64,p FDR-corr = 0.004)and right paracentral lobule(Paracentral?Lobule?R)(t = 5.99,p FDR-corr = 0.002)compared to SF patients.The Re Ho of RE patients decreased in right angular gyrus(Angular?R)(t = 6.91,p FDR-corr = 0.001)and increased in left calcarine fissure and surrounding cortex(Calcarine?L)(t = 4.44,p FDR-corr = 0.021)and right superior occipital gyrus(Occipital?Sup?R)(t = 6.31,p FDR-corr = 0.021).The f ALFF of RE patients increased in left calcarine fissure and surrounding cortex(Calcarine?L)(t = 4.76,p FDR-corr = 0.049)and left middle occipital gyrus(Occipital?Mid?L)(t = 4.78,p FDR-corr = 0.040).Intranetwork connectivity decreased in ventral attention network(VAN)(t = 6.46,p FDR-corr = 0.015)and increased in vision network(VN)(t = 5.38,p FDR-corr = 0.002)in RE patients.Internetwork connectivity increased between posterior default network(p DMN)and sensorymotor network(SMN)(t = 3.249,puncorr = 0.005),executive-control network(ECN)and dorsal attention network(DAN)(t = 3.286,puncorr = 0.004),ECN-SMN(t = 4.303,puncorr < 0.001)in RE patients.Conclusion: Compared to SF patients,the right angular gyrus was attenuated and internetwork connectivity was strengthened to compensate for the impairment in RE patients.The alternation indicated the potential pathophysiological changes in RE.